Question

A patient has a genetic disorder that prevents him from synthesizing C8 and C9. What effect does this have on his ability to resist bloodborne Gram- negative and Gram-positive bacteria? What would happen if \(\mathrm{C} 3\) and \(\mathrm{C} 5\) fragments were also inactivated?

Short answer

A patient unable to synthesize C8 and C9 would have reduced ability to resist Gram-negative bacteria due to impaired MAC formation. Resistance to Gram-positive bacteria would be less affected. If C3 and C5 are also inactivated, the ability to resist both Gram-negative and Gram-positive bacteria would be further reduced due to lack of opsonization and chemotaxis.

Step-by-step solution

Understanding Complements C8 and C9

Complement C8 and C9 are responsible for the formation of Membrane Attack Complex (MAC) on the surface of the pathogen. MAC formation is directly linked with the ability of the immune system to counter gram-negative bacteria by destroying their cell walls and causing cell lysis. If C8 and C9 are not synthesized, MAC formation would be impaired, reducing the effectiveness against Gram-negative bacteria.

Complements Against Gram-positive Bacteria

Gram-positive bacteria are resistant to MAC due to the nature of their cell walls, thus the absence of C8 and C9 would have a lesser impact on resistance to Gram-positive bacteria.

Understanding Complements C3 and C5

Complement C3 and C5 are involved in the initiation and amplification of the immune responses, activation of inflammation, and recruitment of immune cells to the site of infection. If C3 and C5 fragments are inactivated, this will significantly weaken overall immune responses since C3 is involved in opsonization and C5 in the recruitment of phagocytes.

Impact of C3 and C5 Inactivation

C3 and C5 inactivation would significantly reduce the effectiveness of both the classical and alternative pathways of the complement system. This would reduce resistance to both gram-negative and gram-positive bacteria as it would limit both opsonization and chemotaxis processes.

Key concepts

Membrane Attack Complex

The Membrane Attack Complex (MAC) is a vital component of the immune system's defense against bacterial infections. It is a structure formed by proteins in the complement system, specifically: C5b, C6, C7, C8, and C9. The creation of MAC allows the immune system to target and rupture the cell membranes of pathogens.

By puncturing the cell wall, the MAC induces lysis, effectively neutralizing the threat posed by the bacteria. This function is especially important for targeting Gram-negative bacteria, which possess thinner cell walls.

• MAC consists of a series of proteins that assemble to create a pore in the pathogen's membrane.
• Its formation leads to cell death and is a crucial mechanism in defending against infections.

The lack of C8 and C9, however, hampers the formation of the MAC, rendering individuals more susceptible to specific bacterial invasions.

Gram-negative bacteria

Gram-negative bacteria are characterized by their unique cell wall structure, which consists of a thin peptidoglycan layer surrounded by an outer membrane. This outer membrane contains lipopolysaccharides, which can trigger strong immune responses.

Gram-negative bacteria are especially vulnerable to the complement system's Membrane Attack Complex. When MAC disrupts their cell membranes, it causes cell lysis and death.

• They possess an outer membrane that helps resist some antibiotics and detergents.
• The complement system is a critical defense against these types of bacteria.

In situations where essential complement proteins like C8 and C9 are missing, the immune system's ability to fight Gram-negative bacteria is significantly reduced.

Gram-positive bacteria

Gram-positive bacteria have a thick peptidoglycan cell wall followed by a single plasma membrane. This structure makes them more resistant to the Membrane Attack Complex since MAC cannot easily reach their plasma membrane to cause lysis.

Despite being less affected by the absence of C8 and C9, Gram-positive bacteria can still be targeted by other aspects of the immune system.

• They are less susceptible to MAC due to their thick cell wall.
• Other immune functions, such as phagocytosis, still target these bacteria.

Therefore, while the lack of MAC formation has limited consequences on Gram-positive bacteria, other immune pathways play a role in their elimination.

Complement C3

Complement C3 is a crucial part of the complement system, which acts as an amplifier of the immune response. It plays a fundamental role in opsonization, marking pathogens for phagocytosis, and activating subsequent immune processes.

The cleavage of C3 into C3a and C3b is vital:

• C3a helps in inflammation and the recruitment of immune cells to the infection site.
• C3b binds to the surface of pathogens, tagging them for destruction by phagocytes.

If C3 fragments were inactivated, the body would struggle to tag pathogens and recruit immune cells, leaving individuals vulnerable to both Gram-negative and Gram-positive bacterial infections.

Complement C5

Complement C5 is another critical protein in the immune complement system, essential for inflammatory responses and MAC formation. Upon cleavage, C5 produces C5a and C5b, which have distinct functions in immunity.

C5a and C5b:

• C5a acts as a potent chemoattractant, drawing phagocytes to the site of infection and promoting inflammation.
• C5b initiates the assembly of the Membrane Attack Complex, crucial for attacking Gram-negative bacteria.

Without C5, the effectiveness of the complement system is diminished, leading to reduced recruitment of immune cells and weakened ability to form MAC, compromising defense against both types of bacteria.